Module Cover - A New Approach to Genotype-Phenotype Studies
نویسندگان
چکیده
Uncovering and interpreting phenotype/genotype relationships are among the most challenging open questions in disease studies. Set cover approaches are explicitly designed to provide a representative set for diverse disease cases and thus are valuable in studies of heterogeneous datasets. At the same time pathway-centric methods have emerged as key approaches that significantly empower studies of genotype-phenotype relationships. Combining the utility of set cover techniques with the power of network-centric approaches, we designed a novel approach that extends the concept of set cover to network modules cover. We developed two alternative methods to solve the module cover problem: (i) an integrated method that simultaneously determines network modules and optimizes the coverage of disease cases. (ii) a two-step method where we first determined a candidate set of network modules and subsequently selected modules that provided the best coverage of the disease cases. The integrated method showed superior performance in the context of our application. We demonstrated the utility of the module cover approach for the identification of groups of related genes whose activity is perturbed in a coherent way by specific genomic alterations, allowing the interpretation of the heterogeneity of cancer cases.
منابع مشابه
Towards uncovering phenotype/genotype relationships and systems level modeling of tumor heterogeneity
Uncovering and interpreting genotype/phenotype relationships are among the most challenging open questions in disease studies. In complex diseases, such as cancer, uncovering of this relationship is complicated by the heterogeneous nature of these diseases. We have recently developed three complementary approaches to address this challenge. First, we utilized interaction network and an informat...
متن کاملTowards prediction and prioritization of disease genes by the modularity of human phenome-genome assembled network
Empirical clinical studies on the human interactome and phenome not only illustrates prevalent phenotypic overlap and genetic overlap between diseases, but also reveals a modular organization of the genetic landscape of human disease, providing new opportunities to reduce the complexity in dissecting the phenotype-genotype association. We here introduce a network-module based method towards phe...
متن کاملCystic fibrosis from genotype to phenotype: review article
Cystic fibrosis (CF) is the most common autosomal recessive genetic disease, which is caused by defection in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. CFTR gene codes chloride channels to modulate the homeostasis of epithelial environments. Defective CFTR affects various organs such as the lungs, pancreas, intestine, liver and skin; however, lung impairment is the mai...
متن کاملTypology of Earth-shelter Architecture in Iran
Earth-Shelter construction is one of the aspects in architecture where the thermal mass of the earth behind the outer walls are applied in order to reduce heat loss and keep the internal temperature at human comfort range. In case of earth-shelter buildings, housing is especially important. As for its applicability the earth-shelter provides good housing. Typological studies of earth-shelter co...
متن کاملAssociation of tcdA+/tcdB+ Clostridium difficile Genotype with Emergence of Multidrug-Resistant Strains Conferring Metronidazole Resistant Phenotype
Background: Reduced susceptibility of Clostridium difficile to antibiotics is problematic in clinical settings. There is new evidence indicating the cotransfer of toxin-encoding genes and conjugative transposons encoding resistance to antibiotics among different C. difficile strains. To analyze this association, in the current study, we evaluated the frequency of toxigenic C. difficile among th...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing
دوره شماره
صفحات -
تاریخ انتشار 2013